【摘要】 目的：研究强的松、强的松龙在10名男性健康志愿者血浆及血中有核细胞内的可逆代谢药代动力学。方法：各受试者按随机交叉设计进行三次试验，分别为：(1)不服用药物；(2)单次口服50mg强的松；(3)单次口服50mg强的松龙。从血样中分离出血浆和有核细胞后用HPLC法测定强的松、强的松龙和可的松的浓度。结果：口服强的松后，血浆中强的松和强的松龙的峰浓度(Cmax)分别为43.0±11.8和443.8±198.3?g·L-1，曲线下面积(AUC)分别为 382±127和2823±943?g·h·L-1。口服强的松龙后，血浆中强的松和强的松龙的Cmax分别为47.2±14.0和538.9±92.4?g·L-1，AUC分别为335±120和3664±1170?g·h·L-1。两次给药后的强的松与强的松龙的AUC比值经统计比较有显著差异(口服强的松时为7.44±0.64，口服强的松龙时为11.01±0.57，P<0.01)。其余药代动力学参数如表观分布容积(Vd)、清除率(CL)和消除半衰期(T1/2)按照可逆代谢非房室模型进行计算，结果表明强的松的可逆代谢和其他消除过程均比强的松龙快。强的松与强的松龙相互转化的循环分数(RF)为0.68 ± 0.08，口服强的松后，血中有核细胞内强的松和强的松龙的Cmax分别为0.90±0.27和8.93±1.78?g·10-9细胞，而口服强的松龙时，相应的Cmax分别为0.83±0.32和9.26±3.71?更多还原

【Abstract】 OBJECTIVE: To investigate reversible metabolic pharmacokinetics of prednisone and prednisolone in plasma and blood nucleated cells in 10 healthy male volunteers. METHODS: Each subject participated in a three-phase randomed crossover study. The three phases were (1) no drug administration, (2) oral administration of a single 50-mg prednisone, and (3) oral administration of a single 50-mg prednisolone. The plasma and nucleated cells were separated from blood for HPLC analysis of prednisone, prednisolone and cortisol. RESULTS: After administration of prednisone, The maximum plasma concentrations (Cmax) of prednisone and prednisolone were 43.0±11.8 and 443.8±198.3 ?g.L-1, respectively. The areas under concentration-time curve (AUC) of prednisone and prednisolone were 382±127 and 2823±943?g.h.L-1, respectively. After administration of prednisolone, The Cmax of prednisone and prednisolone were 47.2±14.0 and 538.9 ±92.4?g.L-1, respectively. The AUC of prednisone and prednisolone were 335±120 and 3664±1170?g.h.L-1, respectively. There were statistically significant differences in AUC ratio of prednisolone to prednisone for both doses (7.44±0.64 vs. 11.01±0.57, P < 0.01). Other pharmacokinetic parameters, such as volume of distribution (Vd), clearance (CL), elimination half-life (T1/2), were calculated according to a reversible metabolic non-compartment model. It appears from these parameter values that the reversible metabolism and other eliminations of prednisone are faster than those of prednisolone. The fraction recycled through interconversion (RF) was 0.68±0.08, After administration of prednisone, the Cmax of prednisone and prednisolone in blood nucleated cells were 0.90±0.27 and 8.93±1.78 ?g.10-9 cells, respectively. After administration of prednisolone, the Cmax of prednisone and prednisolone in cells were 0.83±0.32 and 9.26±3.71?g.10-9 cells, respectively. There was a significant correlation between plasma concentrations and blood nucleated cells concentrations, which suggested prednisone and prednisolone transfer into cells by passive diffusion. The of prednisolone in cells (2.11±0.67 and 2.57±0.35 h, after administration of prednisone and prednisolone respectively) were significantly (P< 0.01) shorter than either of prednisone in cells (4.28±1.03 and 4.20±0.95 h, after administration of prednisone and prednisolone respectively) or of prednisolone in plasma (5.31±2.26 h). CONCLUSION: The interconversion between prednisone and prednisolone might be a nonlinear process and it is the most primary elimination process in human as well. The pharmacokinetics of prednisolone in cells is not fully consistent with that in plasma.更多还原